a-standardized-protocol-for-functional-motor-mapping-using-navigated

A Standardized Protocol for Functional Motor Mapping Using Navigated Transcranial Magnetic Stimulation

Navigated transcranial magnetic stimulation (nTMS) is based on the integration of individual brain imaging data to determine the precise positioning of ...

Paris Est Créteil University

Paris Est Creteil University

Henri Mondor University Hospital, APHP

Pharmacological neuromodulation strategies have shown limited efficacy in treating memory deficits related to Alzheimer's disease (AD). Despite encouraging results from a few preclinical studies, clinical trials investigating open-loop deep brain stimulation (DBS) for AD have not been successful. Recent refinements in understanding the various phases of memory processes, animal studies investigating phase-specific modulation of hippocampal activity during memorization, and clinical studies using closed-loop DBS strategies to treat patients with movement disorders, all point to the need to investigate closed-loop fornical DBS strategies to better understand memory dynamics and potentially treat memory deficits in AD preclinical models.

Fornical Closed-Loop Stimulation for Alzheimer's Disease.

Optical coherence tomography can differentiate brain regions with intrinsic contrast and at a micron scale resolution. Such a device can be particularly useful as a real-time neurosurgical guidance tool. We present, to our knowledge, the first full-field swept-source optical coherence tomography system operating near a wavelength of 1310 nm. The proof-of-concept system was integrated with an endoscopic probe tip, which is compatible with deep brain stimulation keyhole neurosurgery. Neuroimaging experiments were performed on ex vivo brain tissues and in vivo in rat brains. Using classification algorithms involving texture features and optical attenuation, images were successfully classified into three brain tissue types.

Full-field swept-source optical coherence tomography and neural tissue classification for deep brain imaging.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder featuring repetitive intrusive thoughts and behaviors associated with a significant handicap. Of patients, 20% are refractory to medication and cognitive behavioral therapy. Refractory OCD is associated with suicidal behavior and significant degradation of social and professional functioning, with high health costs. Deep brain stimulation (DBS) has been proposed as a reversible and controllable method to treat refractory patients, with meta-analyses showing 60% response rate following DBS, whatever the target: anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), nucleus accumbens (NAcc), anteromedial subthalamic nucleus (amSTN), or inferior thalamic peduncle (ITP). But how do we choose the "best" target? Functional neuroimaging studies have shown that ALIC-DBS requires the modulation of the fiber tract within the ventral ALIC  the ventral striatum, bordering the bed nucleus of the stria terminalis and connecting the medial prefrontal cortex with the thalamus to be successful. VC/VS effective sites of stimulation were found within the VC and primarily connected to the medial orbitofrontal cortex (OFC) dorsomedial thalamus, amygdala, and the habenula. NAcc-DBS has been found to reduce OCD symptoms by decreasing excessive fronto-striatal connectivity between NAcc and the lateral and medial prefrontal cortex. The amSTN effective stimulation sites are located at the inferior medial border of the STN, primarily connected to lateral OFC, dorsal anterior cingulate, and dorsolateral prefrontal cortex. Finally, ITP-DBS recruits a bidirectional fiber pathway between the OFC and the thalamus. Thus, these functional connectivity studies show that the various DBS targets lie within the same diseased neural network. They share similar efficacy profiles on OCD symptoms as estimated on the Y-BOCS, the amSTN being the target supported by the strongest evidence in the literature. VC/VS-DBS, amSTN-DBS, and ALIC-DBS were also found to improve mood, behavioral adaptability and potentially both, respectively. Because OCD is such a heterogeneous disease with many different symptom dimensions, the ultimate aim should be to find the most appropriate DBS target for a given refractory patient. This quest will benefit from further investigation and understanding of the individual functional connectivity of OCD patients.

Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: Towards an Individualized Approach.

Despite claims that lesional mania is associated with right-hemisphere lesions, supporting evidence is scarce, and association with specific brain areas has not been demonstrated. Here, we aimed to test whether focal brain lesions in lesional mania are more often right- than left-sided, and if lesions converge on areas relevant to mood regulation. We thus performed a systematic literature search (PROSPERO registration CRD42016053675) on PubMed and Web-Of-Science, using terms that reflect diagnoses and structures of interest, as well as lesional mechanisms. Two researchers reviewed the articles separately according to PRISMA Guidelines, selecting reports of adult-onset hypomania, mania or mixed state following a focal brain lesion, for pooled-analyses of individual patient data. Eligible lesion images were manually traced onto the corresponding MNI space slices, and lesion topography analyzed using standard brain atlases. Using this approach, data from 211 lesional mania patients was extracted from 114 reports. Among 201 cases with focal lesions, more patients had lesions involving exclusively the right (60.7%) than exclusively the left (11.4%) hemisphere. In further analyses of 56 eligible lesion images, while findings should be considered cautiously given the potential for selection bias of published lesion images, right-sided predominance of lesions was confirmed across multiple brain regions, including the temporal lobe, fusiform gyrus and thalamus. These, and several frontal lobe areas, were also identified as preferential lesion sites in comparisons with control lesions. Such pooled-analyses, based on the most comprehensive dataset of lesional mania available to date, confirm a preferential association with right-hemisphere lesions, while suggesting that several brain areas/circuits, relevant to mood regulation, are most frequently affected.

Right-sided brain lesions predominate among patients with lesional mania: evidence from a systematic review and pooled lesion analysis.

BACKGROUNDAlthough mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets.METHODSLesion locations associated with mania were identified using a systematic literature search (n = 41) and mapped onto a common brain atlas. The network of brain regions functionally connected to each lesion location was computed using normative human connectome data (resting-state functional MRI, n = 1000) and contrasted with those obtained from lesion locations not associated with mania (n = 79). Reproducibility was assessed using independent cohorts of mania lesions derived from clinical chart review (n = 15) and of control lesions (n = 490). Results were compared with brain stimulation sites previously reported to induce or relieve mania symptoms.RESULTSLesion locations associated with mania were heterogeneous and no single brain region was lesioned in all, or even most, cases. However, these lesion locations showed a unique pattern of functional connectivity to the right orbitofrontal cortex, right inferior temporal gyrus, and right frontal pole. This connectivity profile was reproducible across independent lesion cohorts and aligned with the effects of therapeutic brain stimulation on mania symptoms.CONCLUSIONBrain lesions associated with mania are characterized by a specific pattern of brain connectivity that lends insight into localization of mania symptoms and potential therapeutic targets.FUNDINGFundação para a Ciência e Tecnologia (FCT), Harvard Medical School DuPont-Warren Fellowship, Portuguese national funds from FCT and Fundo Europeu de Desenvolvimento Regional, Child Neurology Foundation Shields Research, Sidney R. Baer, Jr. Foundation, Nancy Lurie Marks Foundation, Mather's Foundation, and the NIH.

Mapping mania symptoms based on focal brain damage.

Cerebral infections related to the presence of an intraparenchymal intracranial pressure transducer (ICPT) are rare. We assessed the incidence of ICPT-related infections and colonization using culture, molecular biology, and electron microscopy.

Assessment of Bacterial Colonization of Intracranial Pressure Transducers: A Prospective Study.

Correction to: Assessment of Bacterial Colonization of Intracranial Pressure Transducers: A Prospective Study.

 Maximum safe resection of infiltrative brain tumors in eloquent area is the primary objective in surgical neuro-oncology. This goal can be achieved with direct electrical stimulation (DES) to perform a functional mapping of the brain in patients awake intraoperatively. When awake surgery is not possible, we propose a pipeline procedure that combines advanced techniques aiming at performing a dissection that respects the anatomo-functional connectivity of the peritumoral region. This procedure can benefit from intraoperative monitoring with computerized tomography scan (iCT-scan) and brain shift correction. Associated with this intraoperative monitoring, the additional value of preoperative investigation combining brain mapping by navigated transcranial magnetic stimulation (nTMS) with various neuroimaging modalities (tractography and resting state functional MRI) has not yet been reported.  A 42-year-old left-handed man had increased intracranial pressure (IICP), left hand muscle deficit, and dysarthria, related to an infiltrative tumor of the right frontal lobe with large mass effect and circumscribed contrast enhancement in motor and premotor cortical areas. Spectroscopy profile and intratumoral calcifications on CT-scan suggested an WHO grade III glioma, later confirmed by histology. The aforementioned surgical procedure was considered, since standard awake surgery was not appropriate for this patient. In preoperative time, nTMS mapping of motor function (deltoid, first interosseous, and tibialis anterior muscles) was performed, combined with magnetic resonance imaging (MRI)-based tractography reconstruction of 6 neural tracts (arcuate, corticospinal, inferior fronto-occipital, uncinate and superior and inferior longitudinal fasciculi) and resting-state functional MRI connectivity (rs-fMRI) of sensorimotor and language networks. In intraoperative time, DES mapping was performed with motor evoked response recording and tumor resection was optimized using non-rigid image transformation of the preoperative data (nTMS, tractography, and rs-fMRI) to iCT data. Image guidance was updated with correction for brain shift and tissue deformation using biomechanical modeling taking into account brain elastic properties. This correction was done at crucial surgical steps, i.e., when tumor bulged through the craniotomy after dura mater opening and when approaching the presumed eloquent brain regions. This procedure allowed a total resection of the tumor region with contrast enhancement as well as a complete regression of IICP and dysarthria. Hand paresis remained stable with no additional deficit. Postoperative nTMS mapping confirmed the good functional outcome.  This case report and technical note highlights the value of preoperative functional evaluation by nTMS updated intraoperatively with correction of brain deformation by iCT. This multimodal approach may become the optimized technique of reference for patients with brain tumors in eloquent areas that are unsuitable for awake brain surgery.

Case Report: Multimodal Functional and Structural Evaluation Combining Pre-operative nTMS Mapping and Neuroimaging With Intraoperative CT-Scan and Brain Shift Correction for Brain Tumor Surgical Resection.

Deep brain stimulation paradigms might be used to treat memory disorders in patients with stroke or traumatic brain injury. However, proof of concept studies in animal models are needed before clinical translation. We propose here a comprehensive review of rodent models for Traumatic Brain Injury and Stroke. We systematically review the histological, behavioral and electrophysiological features of each model and identify those that are the most relevant for translational research.

Rodent models used in preclinical studies of deep brain stimulation to rescue memory deficits.

Gliomas with FGFR3::TACC3 fusion mainly occur in adults, display pathological features of glioblastomas (GB) and are usually classified as glioblastoma, IDH-wildtype. However, cases demonstrating pathological features of low-grade glioma (LGG) lead to difficulties in classification and clinical management. We report a series of 8 GB and 14 LGG with FGFR3:TACC3 fusion in order to better characterize them.

Clinico-pathological and epigenetic heterogeneity of diffuse gliomas with FGFR3::TACC3 fusion.

The authors report a rare case of most likely radiation-induced glioma (RIG) with epithelioid features and the presence of molecular features consistent with RIG. This occurred 70 years after craniofacial brachytherapy. Such a late development of radiation-induced glioblastoma (RIGBM) and the advanced age of presentation for an epithelioid glioblastoma are both unique in the literature. Despite not receiving the full course of adjuvant chemotherapy after surgery and radiotherapy, the patient displayed no signs of recurrence during a 5-year follow-up. RIGBM should be further studied to reveal potential unique clinical and molecular characteristics, as well as to better predict survival and treatment response.

Epithelioid glioblastoma diagnosed 70 years after craniofacial radiotherapy.

Electroencephalography (EEG)-guided neurofeedback (NFB) is a rarely evaluated neuromodulation technique for the treatment of chronic neuropathic pain.

Article	Year
Fornical Closed-Loop Stimulation for Alzheimer's Disease. Trends in neurosciences\| PubMed ID: 29735372	2018
Full-field swept-source optical coherence tomography and neural tissue classification for deep brain imaging. Journal of biophotonics\| PubMed ID: 31710771	2020
Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: Towards an Individualized Approach. Frontiers in psychiatry\| PubMed ID: 31920754	2019
Right-sided brain lesions predominate among patients with lesional mania: evidence from a systematic review and pooled lesion analysis. Translational psychiatry\| PubMed ID: 32398699	2020
Mapping mania symptoms based on focal brain damage. The Journal of clinical investigation\| PubMed ID: 32831292	2020
Assessment of Bacterial Colonization of Intracranial Pressure Transducers: A Prospective Study. Neurocritical care\| PubMed ID: 32929599	2021
Correction to: Assessment of Bacterial Colonization of Intracranial Pressure Transducers: A Prospective Study. Neurocritical care\| PubMed ID: 33063265	2020
Case Report: Multimodal Functional and Structural Evaluation Combining Pre-operative nTMS Mapping and Neuroimaging With Intraoperative CT-Scan and Brain Shift Correction for Brain Tumor Surg... Frontiers in human neuroscience\| PubMed ID: 33716700	2021
Rodent models used in preclinical studies of deep brain stimulation to rescue memory deficits. Neuroscience and biobehavioral reviews\| PubMed ID: 34437937	2021
Clinico-pathological and epigenetic heterogeneity of diffuse gliomas with FGFR3::TACC3 fusion. Acta neuropathologica communications\| PubMed ID: 36647073	2023
Epithelioid glioblastoma diagnosed 70 years after craniofacial radiotherapy. Acta neurochirurgica\| PubMed ID: 37269332	2023
Relieving Chronic Neuropathic Pain With EEG-Neurofeedback. European journal of neurology\| PubMed ID: 40947911	2025

Suhan Senova

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